The overall goals of this project are to understand how plasticity in motor cortex (MI) participates in motor skill acquisition and to identify mechanisms for synaptic modification that operate in MID during learning. Initial work demonstrating rapid plasticity in adult rat MI representations suggested a role for MI in motor learning. Subsequent demonstration of a horizontal connectional network within MI capable of long term potentiation (LTP) and depression (LTD), suggested that these pathways contribute to learning- associated plasticity. Now, modifications in the efficacy of MI horizontal connections and in the amount of LTP have been found after five days of forelimb pellet-retrieval training. Because these changes can be detected in recording made from cortical slice preparations, well-controlled analysis of the learning-induced changes within MI circuits are possible. The goals of the present study are to show how modifications in the efficacy of MI horizontal connections are associated with skill learning and to determine which mechanisms are engaged by learning to modify MI circuits. Aim 1 is to establish learning curves for motor skill acquisition and correlate them with strength changes within MI horizontal connections following different amounts of training. Aim 2 is to determine the specificity of synaptic modifications to layer II-III connections in MI by examining learning effects upon other MI pathways an in another cortical area. The ability to evaluate multiple pathways simultaneously in slices will be enhanced by using novel multichannel electrode arrays. Aim 3 comprises three sets of experiments designed to examine the role of activity-dependent mechanisms within MI for learning. First, the requirement for LTP in skill acquisition will be tested by depotentiating MI horizontal connections in vivo following training. Second, the use of LTP by learning will be evaluated by testing the ability of learning to occlude electrically-induced LTP. Third, the hypothesis will be tested that the same molecular markers will be expressed with learning and with modifications in MI. Together, these studies will help to clarify the role of MI in skill acquisition and may establish a model in which learning can be directly related to synaptic modifications in cortex. These results may also provide a basis for new regiments that promote beneficial reorganization or cortex after damage by showing how activity and specific mechanisms participate in restructuring cortical organization.